Phase II Study of the Combination of Low-Intensity Chemotherapy and Blinatumomab in Patients With Philadelphia Chromosome Negative Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Event Free Survival (EFS) Where Events Defined as no Response, Loss of Response, or Death
研究概览
简要总结
This phase II trial studies how well low-intensity chemotherapy and blinatumomab work in treating patients with Philadelphia chromosome negative acute lymphoblastic leukemia that has come back or does not respond to treatment. Drugs used in chemotherapy, such as dexamethasone, filgrastim, pegfilgrastim, cyclophosphamide, methotrexate, cytarabine and vincristine sulfate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as blinatumomab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving low-intensity chemotherapy and blinatumomab may work better at treating acute lymphoblastic leukemia.
详细描述
PRIMARY OBJECTIVE:
I. To evaluate the combined effect of blinatumomab and mini-hyper-CVD (low-intensity chemotherapy) on event-free survival.
SECONDARY OBJECTIVES:
I. Evaluating other clinical efficacy endpoints (minimal residual disease [MRD] negativity, duration of response, the overall response rate [complete response (CR) + CR with inadequate count recovery (CRi)]) of the regimen occurred any time during the treatment.
II. Overall survival. III. Determining the safety of the combination regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with first or second relapsed/refractory B-cell acute lymphoblastic leukemia (ALL)
- •Performance status =< 3 (Eastern Cooperative Oncology Group [ECOG] scale)
- •Total serum bilirubin =< 2 x upper limit of normal (ULN), unless due to Gilbert's syndrome, hemolysis or the underlying leukemia approved by the principal investigator (PI)
- •Alanine aminotransferase (ALT) =< 3 x ULN, unless due to the underlying leukemia approved by the PI
- •Aspartate aminotransferase (AST) =< 3 x ULN unless due to the underlying leukemia approved by the PI
- •Signed informed consent
- •Women of childbearing potential (WOCBP) or male subjects with a partner who is WOCBP must agree to use contraception during the study, if sexually active
排除标准
- •Patients with Philadelphia chromosome (Ph)-positive ALL or Burkitt leukemia
- •Active, uncontrolled central nervous system (CNS) leukemia involvement
- •Active serious infection not controlled by oral or intravenous antibiotics
- •Active secondary malignancy other than skin cancer (e.g., basal cell carcinoma or squamous cell carcinoma) that in the investigator's opinion will shorten survival to less than 1 year
- •Known hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV)
- •Active grade III-V cardiac failure as defined by the New York Heart Association criteria
- •Patients with a cardiac ejection fraction (as measured by either multi-gated acquisition [MUGA] or echocardiogram) < 40%
- •Prior history of treatment with blinatumomab
- •Treatment with any investigational antileukemic agents or chemotherapy agents in the last two weeks, unless full recovery from side effects has occurred or patient has rapidly progressive disease judged to be life-threatening by the investigator
- •Pregnant and lactating women will not be eligible; women of childbearing potential should have a negative pregnancy test prior to entering on the study and be willing to practice methods of contraception; women do not have childbearing potential if they have had a hysterectomy or are postmenopausal without menses for 12 months; in addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control
研究组 & 干预措施
Treatment (blinatumomab, combination chemotherapy)
See detailed description.
干预措施: Blinatumomab (Biological)
Treatment (blinatumomab, combination chemotherapy)
See detailed description.
干预措施: Cyclophosphamide (Drug)
Treatment (blinatumomab, combination chemotherapy)
See detailed description.
干预措施: Cytarabine (Drug)
Treatment (blinatumomab, combination chemotherapy)
See detailed description.
干预措施: Dexamethasone (Drug)
Treatment (blinatumomab, combination chemotherapy)
See detailed description.
干预措施: Filgrastim (Biological)
Treatment (blinatumomab, combination chemotherapy)
See detailed description.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (blinatumomab, combination chemotherapy)
See detailed description.
干预措施: Leucovorin Calcium (Drug)
Treatment (blinatumomab, combination chemotherapy)
See detailed description.
干预措施: Mercaptopurine (Drug)
Treatment (blinatumomab, combination chemotherapy)
See detailed description.
干预措施: Methotrexate (Drug)
Treatment (blinatumomab, combination chemotherapy)
See detailed description.
干预措施: Pegfilgrastim (Biological)
Treatment (blinatumomab, combination chemotherapy)
See detailed description.
干预措施: Rituximab (Biological)
Treatment (blinatumomab, combination chemotherapy)
See detailed description.
干预措施: Vincristine Sulfate (Drug)
结局指标
主要结局
Event Free Survival (EFS) Where Events Defined as no Response, Loss of Response, or Death
时间窗: Time from the first day of treatment assessed up to 3 years, 1 month
Time from date of treatment start until the date of first objective documentation of disease-relapse. Relapse and resistant disease will be defined based on morphological assessment of bone marrow and peripheral blood. Complete Remission (CR): Normalization of the peripheral blood and bone marrow with 5% or less blasts in normocellular or hypercellular marrow with a granulocyte count of 1 x 10\^9/L or above, and platelet count of 100 x 10\^9/L. Complete resolution of all sites of extramedullary disease is required for CR. Complete remission without recovery of counts (CRi): Peripheral blood and marrow results as for CR, but with incomplete recover of counts (platelets \< 100 x 10\^9/L; neutrophils \< 1 x 10\^9/L). Partial Response (PR): As above for CR except for the presence of 6-25% marrow blasts.
次要结局
- Overall Survival(Time from the first day of treatment assessed up to 3 years, 1 month)
- Participants With a Response(Up to 3 years)
- Duration of Response(Time from the first day of treatment assessed up to 3 years, 1 month)
- Number of Participants Negative for Minimal Residual Disease (MRD)(Up to 3 years)